{"id":"f1030c5b-e1e2-59c8-8548-ada5572370e3","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-methyl-mtr-ko-trap","predicate":"loss_traps","statement":"MTR knockout in tumour cells using physiological extracellular folates caused trapping and limited assimilation into other folate forms.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"f9f8083a-0896-55f6-8b29-6d6cdd0d9f79","mechanism_event_label":"Methylfolate still needs MTR for reuse.","subject":{"id":"3237350f-4568-57e6-a1db-d5d41d1a98a7","slug":"mtr-human-gene","display_name":"MTR gene (Homo sapiens)","entity_type_key":"gene"},"object":{"id":"23f48782-478e-5f62-874a-31273c075fe7","slug":"5-methyltetrahydrofolate","display_name":"5-Methyltetrahydrofolate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"f9f8083a-0896-55f6-8b29-6d6cdd0d9f79","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-methyl-mtr-ko-trap-event","event_type":"biochemical_relationship","label":"Methylfolate still needs MTR for reuse.","description":"MTR knockout in tumour cells using physiological extracellular folates caused trapping and limited assimilation into other folate forms.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"91aa077a-bfee-574d-9e5f-28da25239196","slug":"mtr","display_name":"Cobalamin-dependent methionine synthase / MTR","entity_type_key":"protein"},"role":"deleted enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d2b23343-c688-5fc3-9f42-bfac0050552b","slug":"tetrahydrofolate","display_name":"Tetrahydrofolate","entity_type_key":"small_molecule"},"role":"recycled folate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"3237350f-4568-57e6-a1db-d5d41d1a98a7","slug":"mtr-human-gene","display_name":"MTR gene (Homo sapiens)","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"23f48782-478e-5f62-874a-31273c075fe7","slug":"5-methyltetrahydrofolate","display_name":"5-Methyltetrahydrofolate","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"Methylfolate does not remove the B12-dependent MTR requirement.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Ghergurovich 2021 Fig. 3A; physiological folate experiments Fig. 2 and Extended Data Fig. 2.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Isotope tracing in tumour cells, mouse tissues and xenografts.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"CRISPR MTR deletion; folic acid or 5-methyl-THF medium; physiological folate-mixture experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Nutrient environment matters.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"folate","display_name":"Folate (vitamin B9)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Methylfolate still needs MTR for reuse.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ghergurovich-2021] Methionine synthase supports tumour tetrahydrofolate pools (2021). https://pubmed.ncbi.nlm.nih.gov/34799699/ DOI: 10.1038/s42255-021-00465-w","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HCT116 human colorectal cancer cells (folate profiling)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"b9e5489c-eaa8-594e-ac19-dae5941e115e","evidence_kind":"source_excerpt","locator":"Lines 517-529","start_line":517,"end_line":529,"excerpt":"### folate-methyl-mtr-ko-trap\nMTR knockout in tumour cells using physiological extracellular folates caused trapping and limited assimilation into other folate forms.\nCondition category: machinery_impairment\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Methylfolate still needs MTR for reuse.\norganism: Homo sapiens\ntissue_or_cell_type: HCT116 human colorectal cancer cells (folate profiling)\nexperimental_model: Isotope tracing in tumour cells, mouse tissues and xenografts.\nlimitations: Nutrient environment matters.\ncross_nutrient: Methylfolate does not remove the B12-dependent MTR requirement.\nexposure: CRISPR MTR deletion; folic acid or 5-methyl-THF medium; physiological folate-mixture experiments\nevidence_location: Ghergurovich 2021 Fig. 3A; physiological folate experiments Fig. 2 and Extended Data Fig. 2.\n[ghergurovich-2021] Methionine synthase supports tumour tetrahydrofolate pools (2021). https://pubmed.ncbi.nlm.nih.gov/34799699/ DOI: 10.1038/s42255-021-00465-w","model_system":"Isotope tracing in tumour cells, mouse tissues and xenografts.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ghergurovich-2021] Methionine synthase supports tumour tetrahydrofolate pools (2021). https://pubmed.ncbi.nlm.nih.gov/34799699/ DOI: 10.1038/s42255-021-00465-w","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f4ce1a62-9582-5f7a-84f5-a23d0e1bfc68","stable_key":"import-ec174d5a-4903-5745-8646-df0e9d4265e8","title":"Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"e564d43989ece1006c95cd0748e9af6fe369074599a2eebba0a99ebff864b0dd","revision_id":"76674a33-b2a1-5e41-b71b-44399038ff7c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}